2-Aminoadipic acid protects against obesity and diabetes

in Journal of Endocrinology
Authors:
Wang-Yang Xu State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Biotecan Medical Diagnostics Co., Ltd, Zhangjiang Center for Translational Medicine, Shanghai, China

Search for other papers by Wang-Yang Xu in
Current site
Google Scholar
PubMed Close
,
Yan Shen State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Search for other papers by Yan Shen in
Current site
Google Scholar
PubMed Close
,
Houbao Zhu State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Search for other papers by Houbao Zhu in
Current site
Google Scholar
PubMed Close
,
Junhui Gao Biotecan Medical Diagnostics Co., Ltd, Zhangjiang Center for Translational Medicine, Shanghai, China

Search for other papers by Junhui Gao in
Current site
Google Scholar
PubMed Close
,
Chen Zhang Biotecan Medical Diagnostics Co., Ltd, Zhangjiang Center for Translational Medicine, Shanghai, China

Search for other papers by Chen Zhang in
Current site
Google Scholar
PubMed Close
,
Lingyun Tang State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Search for other papers by Lingyun Tang in
Current site
Google Scholar
PubMed Close
,
Shun-Yuan Lu State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Search for other papers by Shun-Yuan Lu in
Current site
Google Scholar
PubMed Close
,
Chun-Ling Shen State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Search for other papers by Chun-Ling Shen in
Current site
Google Scholar
PubMed Close
,
Hong-Xin Zhang State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Search for other papers by Hong-Xin Zhang in
Current site
Google Scholar
PubMed Close
,
Ziwei Li Biotecan Medical Diagnostics Co., Ltd, Zhangjiang Center for Translational Medicine, Shanghai, China

Search for other papers by Ziwei Li in
Current site
Google Scholar
PubMed Close
,
Peng Meng Biotecan Medical Diagnostics Co., Ltd, Zhangjiang Center for Translational Medicine, Shanghai, China

Search for other papers by Peng Meng in
Current site
Google Scholar
PubMed Close
,
Ying-Han Wan Shanghai Research Center for Model Organisms, Shanghai, China

Search for other papers by Ying-Han Wan in
Current site
Google Scholar
PubMed Close
,
Jian Fei Shanghai Research Center for Model Organisms, Shanghai, China

Search for other papers by Jian Fei in
Current site
Google Scholar
PubMed Close
, and
Zhu-Gang Wang State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai Research Center for Model Organisms, Shanghai, China
Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China

Search for other papers by Zhu-Gang Wang in
Current site
Google Scholar
PubMed Close

Correspondence should be addressed to Z-G Wang: zhugangw@shsmu.edu.cn

*(W-Y Xu, Y Shen and H Zhu contributed equally to this work)

DOI:
https://doi.org/10.1530/JOE-19-0157
Volume/Issue:
Volume 243: Issue 2
Article Type:
Research Article
Page Range:
111–123
Online Publication Date:
Nov 2019
Copyright:
© 2019 Society for Endocrinology 2019
Restricted access
Rent on DeepDyve

Sign up for journal news

Obesity and type 2 diabetes (T2D) are both complicated endocrine disorders resulting from an interaction between multiple predisposing genes and environmental triggers, while diet and exercise have key influence on metabolic disorders. Previous reports demonstrated that 2-aminoadipic acid (2-AAA), an intermediate metabolite of lysine metabolism, could modulate insulin secretion and predict T2D, suggesting the role of 2-AAA in glycolipid metabolism. Here, we showed that treatment of diet-induced obesity (DIO) mice with 2-AAA significantly reduced body weight, decreased fat accumulation and lowered fasting glucose. Furthermore, Dhtkd1−/− mice, in which the substrate of DHTKD1 2-AAA increased to a significant high level, were resistant to DIO and obesity-related insulin resistance. Further study showed that 2-AAA induced higher energy expenditure due to increased adipocyte thermogenesis via upregulating PGC1α and UCP1 mediated by β3AR activation, and stimulated lipolysis depending on enhanced expression of hormone-sensitive lipase (HSL) through activating β3AR signaling. Moreover, 2-AAA could alleviate the diabetic symptoms of db/db mice. Our data showed that 2-AAA played an important role in regulating glycolipid metabolism independent of diet and exercise, implying that improving the level of 2-AAA in vivo could be developed as a strategy in the treatment of obesity or diabetes.

Supplementary Materials

    • Supplementary Fig. 1
    • Supplementary Fig. 2
    • Supplementary Fig. 3
    • Supplementary Fig. 4
    • Supplementary Fig. 5
    • Supplementary Fig. 6
    • Supplementary Fig. 7
    • Supplementary Fig. 8
    • Supplementary Fig. 9
    • Supplementary Fig. 10
    • Supplementary Fig. 11
    • Supplementary Fig. 12
    • Supplementary Fig. 13
    • Table S1. Specific primers for quantitative RT-PCR.

Journal of Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 1196 133 2
PDF Downloads 876 140 2

 

  • Collapse
  • Expand
Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2019 Society for Endocrinology 2019
Page(s):
13
Article Type:
Research Article
Received Date:
28 Jul 2019
Accepted Date:
20 Aug 2019
Print Publication Date:
01 Nov 2019
Online Publication Date:
Nov 2019
Keywords:
2-aminoadipic acid; obesity; diabetes; β3 adrenergic receptor; thermogenesis; lipolysis